A peritoneal dialysis therapy which is one of the symptomatic therapies for renal failure has attracted attention as one of home medical cares, since the device and implement do not become large in scale as compared with a dialysis therapy performed through an artificial kidney and also there are few temporal restrictions. Many of currently-used peritoneal dialysis fluids use glucose as an osmotic agent. Glucose has an advantage of being relatively safe, and being inexpensive; however, a continuous dehydration effect cannot be obtained because glucose has a small molecular weight and is rapidly absorbed from the peritoneum. From the above situation, an investigation of an osmotic agent that can maintain ultrafiltration during long-term storage in place of glucose was performed, and it has been found that icodextrin, a glucose polymer, is suitable for a peritoneal dialysis fluid.
Icodextrin is not rapidly absorbed via the peritoneum due to a large molecular weight, and acts mainly as a colloid osmotic agent, and a dehydration effect can be obtained while maintaining the osmotic pressure with blood plasma. Currently, in a peritoneal dialysis fluid in which icodextrin is used, a medical solution is prescribed to be in the range of pH 5.0 to 5.5 in order to prevent the decomposition and coloring of the icodextrin.
According to a recent study, it has been reported that a peritoneal dialysis fluid having such a pH substantially lowers the immunological defense mechanism for a peritoneal macrophage, and increases the risk of peritonitis against the ingress of bacteria. Furthermore, it has been reported that in a peritoneal dialysis fluid of pH 5.0 to 5.5, damage to cultured peritoneal mesothelial cells is significantly high, and it is effective for reducing the damage that the pH of the peritoneal dialysis fluid is 6.5 or more.
However, the pH of a peritoneal dialysis fluid has a significant impact on the stability of icodextrin; when the pH is increased without changes, the icodextrin is decomposed into glucose at the time of manufacture or storage, the peritoneal dialysis fluid is colored by the deterioration of the glucose, and then the product value is significantly lowered. That is, the absorbance of 284 nm, which is an index of 5-hydroxymethylfurfural which is a main decomposition product of glucose, is successively increased.
Therefore, as a method of increasing the pH of the peritoneal dialysis fluid while suppressing the decomposition and coloring of the icodextrin, a pharmaceutical preparation has been developed, in which an icodextrin and a liquid medicine component having high pH are separately stored until a time for use and are aseptically mixed immediately before use (Patent Literature 1).
However, requirement for the stability of peritoneal dialysis fluid and the safety of peritoneal dialysis fluid increasingly becomes high-dimensional in recent years, and a development of a stable peritoneal dialysis fluid has been desired, in which a pH is in the physiological range which does not affect on human bodies, and the decomposition of icodextrin into glucose and the coloring of icodextrin are suitably suppressed.